Low-Fluence Photodynamic Therapy versus Ranibizumab for Chronic Central Serous Chorioretinopathy: One-Year Results of a Randomized Trial

doi:10.1016/j.ophtha.2013.09.024

Ophthalmology

Volume 121, Issue 2, February 2014, Pages 558-565

https://doi.org/10.1016/j.ophtha.2013.09.024 Get rights and content

Purpose

To compare the efficacy and safety between low-fluence photodynamic therapy (PDT) and the intravitreal ranibizumab in the treatment of chronic central serous chorioretinopathy (CSC).

Design

Prospective, randomized, single-center, parallel-arm, controlled trial.

Participants

Thirty-four eyes of 32 patients with chronic CSC with >6 months' duration of symptoms or recurrent CSC were randomly placed into the low-fluence PDT group (n = 18) or the ranibizumab group (n = 16).

Intervention

The patients underwent a single session of low-fluence PDT or 3 consecutive monthly injections of ranibizumab. Rescue treatment was available from month 3 if the subretinal fluid (SRF) persisted or recurred after primary treatment; low-fluence PDT was given to the ranibizumab group and intravitreal ranibizumab to the low-fluence PDT group.

Main Outcome Measures

The primary outcome was the proportion of eyes with complete resolution of SRF without rescue treatment. Secondary outcomes included the mean changes in logarithm of the minimum angle of resolution best-corrected visual acuity (BCVA), central retinal thickness (CRT), and angiographic findings from baseline to 12 months.

Results

At month 12, 16 eyes (88.9%) of the low-fluence PDT group maintained complete resolution of SRF without rescue treatment versus 2 eyes (12.5%) in the ranibizumab group (P <0.001). Two eyes (11.1%) in the low-fluence PDT group and 11 eyes (68.8%) in the ranibizumab group met the criteria for rescue treatment (P = 0.001). In the low-fluence PDT group, the mean decrease in CRT from baseline was significantly greater than that in the ranibizumab group until month 6 (P <0.05), but the differences became insignificant thereafter. The improvement in BCVA from baseline was superior in the low-fluence PDT group to that in the ranibizumab group, but the differences were not statistically significant except at month 3 (P = 0.025). On indocyanine green angiography, a significantly greater proportion of the low-fluence PDT group (16 eyes; 88.9%) showed a marked reduction in choroidal hyperpermeability after primary treatment than that of the ranibizumab group (0 eyes; P <0.001). No serious adverse events related to the drugs or procedures were observed.

Conclusions

This study represents the overall superiority of low-fluence PDT compared with intravitreal ranibizumab in the treatment of chronic CSC.

Section snippets

Methods

This prospective, single-center, randomized, parallel-arm, 1-year, controlled clinical trial of the patients with chronic CSC was prospectively approved by the Institutional Review Board and Ethics Committee at Seoul National University Hospital and the Korean Food and Drug Administration. The study was conducted in accordance with the tenets of the Declaration of Helsinki. Written, informed consent was obtained from each participant before enrollment. This study was registered at //clinicaltrial.gov

Results

Thirty-four eyes from 32 patients with chronic CSC were enrolled, of which 18 eyes (52.9%) were randomly placed into the low-fluence PDT group and 16 eyes (47.1%) into the ranibizumab group. All 18 eyes in the low-fluence PDT group completed the 12 months of follow-up. In the ranibizumab group, 2 patients were lost to follow-up at months 4 and 8 owing to refusal of rescue treatment. The mean age of the patients was 50.8±7.7 years (range, 35–65 years), with 26 male (81.3%) and 6 female (18.8%)

Discussion

This clinical trial compared treatment outcomes between low-fluence PDT and intravitreal ranibizumab in patients with chronic CSC. This study demonstrates the overall superiority of low-fluence PDT compared with intravitreal ranibizumab in terms of efficacy outcomes.

Regarding anatomic outcomes, a significantly greater proportion of subjects in the low-fluence PDT group (88.9%) maintained complete resolution of the SRF without rescue treatment compared with the ranibizumab group (12.5%). The

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Cited by (64)

Characteristics Related to Visual Acuity Loss After Successful Photodynamic Therapy for Eyes With Central Serous Chorioretinopathy
2023, American Journal of Ophthalmology
This study aimed to examine baseline characteristics for identifying factors associated with vision loss (VL) in patients with central serous chorioretinopathy (CSC) who successfully responded to photodynamic therapy (PDT).
A retrospective, clinical case-control study.
This study included 85 eyes with CSC, which underwent PDT, and resolved serous retinal detachment. These eyes were classified into 2 groups: the VL group (best-corrected visual acuity 6 months after PDT was worse than that at baseline) and the vision maintenance or improved group (the others). Baseline factors were analyzed to determine the characteristics of the VL group and assess the diagnostic potential of these factors.
Seventeen eyes were included in the VL group. The mean values of the neurosensory retinal (NSR) thickness, the internal limiting membrane–external limiting membrane thickness (IET), and the external limiting membrane–photoreceptor outer segment thickness (EOT) in the VL group were significantly thinner than those in the vision maintenance or improved group (NSR thickness, 123.2 ± 39.7 µm vs 166.3 ± 49.6 µm, P < .001; IET, 63.1 ± 17.0 µm vs 88.0 ± 25.4 µm, P < .001; EOT, 60.1 ± 28.6 µm vs 78.3 ± 33.1, P = .041). The sensitivity, specificity, and positive and negative predictive values for predicting VL were 94.1%, 50.0%, 32.0%, and 97.1% for NSR thickness; 94.1%, 51.5%, 32.7%, and 97.2% for IET; and 94.1%, 30.9%, 25.4%, and 95.5% for EOT, respectively.
Pretreatment sensory retinal layer thickness could predict VL after PDT for CSC and may be a helpful reference for PDT.
A Photodynamic Therapy Index for Central Serous Chorioretinopathy to Predict Visual Prognosis Using Pretreatment Factors
2023, American Journal of Ophthalmology
This study aimed to establish a treatment index based on functional outcomes of photodynamic therapy (PDT) for central serous chorioretinopathy (CSC).
A retrospective clinical case-control study.
This was a single-institute study. Eighty (80) eyes with CSC, who were treated by PDT and whose subretinal fluid resolves within 6 months were divided into two groups: those with poor visual outcome (PVO) (best-corrected visual acuity [BCVA] ≤ 0.5 6 months post-PDT), and the remaining eyes (better visual outcome [BVO]). The areas under the curve (AUC) and cutoff values from receiver operating characteristic curves were examined. These was used to predict the groups using pretreatment BCVA and the thickness of each retinochoroidal layer.
Twenty-one (21) eyes were in the PVO group and 59 eyes in the BVO group were included. The AUCs were 0.959 for BCVA, 0.959 for the thickness from the internal limiting membrane to the external limiting membrane (IET), 0.820 for the thickness from the external limiting membrane to the photoreceptor outer segment layer, 0.715 for the subfoveal retinal thickness, and 0.515 for the subfoveal choroidal thickness. The BCVA and IET cut-off values were 0.267 logMAR and 71.5 µm, respectively. Using the combination of the cutoff values of BCVA and IET, the highest values for the sensitivity, specificity, positive predictive value, and negative predictive value were 95.2%, 94.9%, 85.0%, and 98.0%, respectively.
The combination of pre-PDT BCVA and IET in CSC can accurately predict the post-treatment visual prognosis. These values could be used as a treatment index of PDT for CSC.
Fuji sign: Prevalence and predictive power to photodynamic therapy in chronic central serous chorioretinopathy
2023, Photodiagnosis and Photodynamic Therapy
To determine the prevalence of Fuji sign in central serous chorioretinopathy (cCSC) patients and its predictive power of good response to photodynamic therapy (PDT).
Retrospective study, including 135 eyes of 130 patients diagnosed with cCSC treated with PDT between 2017 and 2021. Optical Coherence Tomography (OCT) images from these patients were compiled and analyzed. The presence of the Fuji sign, an anatomical finding recently described as a predictor of spontaneous resolution of the subretinal fluid (SRF) in cCSC, as assessed in basal images and the maximum height of SRF pre- and post-PDT OCT was measured.
Mean age was 56.6 years, 69.4% were men and the percentage of partial or complete resolution of the SRF after PDT was 75.55%. Only 8.9% of patients (12/135) had positive Fuji sign at baseline OCT. Among them, 50% (6/12) presented a complete response to the PDT (pre-PDT SRF: 109.00 (29.61) µm), 8.3% (1/12) had a partial resolution of the SRF (127 µm to 66 µm) and 41.6% (5/12) did not respond to PDT (pre-PDT SRF: 71.00 (22.82) µm, post-PDT SRF: 83.60 (36.13) µm).
Fuji sign has a low prevalence in cCSC and its presence is not associated with a good response to PDT.
Evaluation of clinical and functional sequels of central serous chorioretinopathy. A case series analysis
2022, Archivos de la Sociedad Espanola de Oftalmologia
Evaluar las secuelas clínicas y funcionales de pacientes con diagnóstico de coriorretinopatía serosa central (CSC) resuelta, mediante OCT macular, prueba de sensibilidad al contraste, campo visual 10-2 y prueba de colores Farnsworth D-15.
Se incluyeron y evaluaron 27 ojos de 26 individuos con CSC resuelta por OCT macular; a los pacientes se les realizó prueba de sensibilidad al contraste con el equipo Optec 6500, campo visual 10-2 con Octopus 900 Haag- Streit y prueba de color Farnsworth D-15.
Se observaron secuelas en 20 ojos (74,1%) por OCT macular y en 21 (77,8%) en la sensibilidad al contraste, predominantemente defecto tipo 2. También 27 (100%) tenían un campo visual 10-2 alterado correspondiente a sensibilidad foveal reducida, y 11 ojos (40,7%) correspondían a escotomas centrales y paracentrales. La prueba de color mostró alteración en 11 (40,7%) del total de ojos evaluados, encontrando tritanomalía en 9 de ellos (81,8%). No se observaron diferencias significativas en los estudios entre el grupo de observación vs el grupo de tratamiento.
La CSC puede dejar secuelas en la calidad visual de los pacientes a pesar de su tratamiento en fase aguda. La agudeza visual antes y después del tratamiento en el grupo de intervención no tuvo diferencia significativa.
To evaluate the clinical and functional sequelae of patients with a diagnosis of resolved central serous chorioretinopathy (CSC), through macular OCT, contrast sensitivity test, visual field 10-2 and Farnsworth D-15 color test.
27 eyes of 26 individuals with CSC resolved by macular OCT were included and evaluated. The patients underwent a contrast sensitivity test with the Optec 6500 equipment, a 10-2 visual field with an Octopus 900 Haag-Streit, and a Farnsworth D-15 color test.
Sequelae were observed in 20 eyes (74.1%) by macular OCT and in 21 (77.8%) in contrast sensitivity, predominantly type 2 defect. Also 27 (100%) had a visual field 10-2 altered corresponding to reduced foveal sensitivity, 11 eyes (40.7%) corresponded to central and paracentral scotomas. The color test showed alteration in 11 (40.7%) of the total eyes evaluated, finding tritanomaly in 9 of them (81.8%). No significant differences were observed in the studies between observation group vs the treatment group.
CSC can leave sequelae in the visual quality of patients despite treatment in the acute phase. Visual acuity before and after treatment in the intervention group had no significant difference.
Effectiveness of Reduced-fluence Photodynamic Therapy for Chronic Central Serous Chorioretinopathy: A Propensity Score Analysis
2022, Ophthalmology Science
To investigate the 2-year effectiveness of reduced-fluence photodynamic therapy (rf-PDT) for chronic central serous chorioretinopathy (cCSC).
Retrospective cohort study.
A total of 223 consecutive patients with newly diagnosed cCSC with active serous retinal detachment (SRD) were included from May 2007 to June 2017 and followed up for at least 2 years. Patients who underwent ocular treatment other than cataract surgery before the beginning of recruitment and those who had macular neovascularization at baseline were excluded.
All patients underwent a comprehensive ophthalmic evaluation, including measurements of best-corrected visual acuity (BCVA), slit-lamp examination, dilated fundus examination, color fundus photography, fundus autofluorescence, fluorescein angiography, indocyanine green angiography, and spectral-domain OCT. An inverse probability of treatment weighting (IPTW) methodology was applied to balance 18 baseline characteristics between patients who received rf-PDT (rf-PDT group) and those who did not receive treatment (controls). Inverse probability of treatment weighting survival analysis and regression were performed.
The proportion of patients whose BCVA at 24 months was the same or improved compared with the baseline visual acuity (VA) (VA maintenance rate).
A total of 155 eyes (rf-PDT group: 74; controls: 81) were analyzed. The patients’ backgrounds were well balanced after IPTW with standardized differences of < 0.10. An IPTW regression analysis revealed that the VA maintenance rate was significantly higher in the rf-PDT group than in the controls (93.6% vs. 70.9%, P < 0.001, 12 months; 85.7% vs. 69.8%, P = 0.019, 24 months). The rf-PDT group tended to show better VA improvement, but was not statistically significant (–0.06 vs. –0.008, P = 0.07, 12 months; –0.06 vs. –0.03, P = 0.32, 24 months). An IPTW Cox regression showed a significantly higher rate of complete SRD remission in the rf-PDT group (hazard ratio, 5.05; 95% confidence interval, 3.24–7.89; P < 0.001).
The study suggests the beneficial effect of rf-PDT for cCSC for both VA maintenance and higher proportion of complete SRD remission in the clinical setting.
Venous overload choroidopathy: A hypothetical framework for central serous chorioretinopathy and allied disorders
2022, Progress in Retinal and Eye Research
Citation Excerpt :
Randomized controlled studies of varying sizes found patients receiving PDT did better than those getting a placebo (Chan et al., 2008; Wu et al., 2011). The trials comparing PDT to anti-vascular endothelial growth factors were underpowered and no conclusions could be made about relative efficacy (Bae et al., 2014; Semeraro et al., 2012). PDT was compared to micro-pulse laser in two trials, both showing improved efficacy with PDT (Kretz et al., 2015; van Dijk et al., 2018).
In central serous chorioretinopathy (CSC), the macula is detached because of fluid leakage at the level of the retinal pigment epithelium. The fluid appears to originate from choroidal vascular hyperpermeability, but the etiology for the fluid is controversial. The choroidal vascular findings as elucidated by recent optical coherence tomography (OCT) and wide-field indocyanine green (ICG) angiographic evaluation show eyes with CSC have many of the same venous patterns that are found in eyes following occlusion of the vortex veins or carotid cavernous sinus fistulas (CCSF). The eyes show delayed choroidal filling, dilated veins, intervortex venous anastomoses, and choroidal vascular hyperpermeability. While patients with occlusion of the vortex veins or CCSF have extraocular abnormalities accounting for the venous outflow problems, eyes with CSC appear to have venous outflow abnormalities as an intrinsic phenomenon. Control of venous outflow from the eye involves a Starling resistor effect, which appears to be abnormal in CSC. Similar choroidal vascular abnormalities have been found in peripapillary pachychoroid syndrome. However, peripapillary pachychoroid syndrome has intervortex venous anastomoses located in the peripapillary region while in CSC these are seen to be located in the macular region. Spaceflight associated neuro-ocular syndrome appears to share many of the pathophysiologic problems of abnormal venous outflow from the choroid along with a host of associated abnormalities. These diseases vary according to their underlying etiologies but are linked by the venous decompensation in the choroid that leads to significant vision loss. Choroidal venous overload provides a unifying concept and theory for an improved understanding of the pathophysiology and classification of a group of diseases to a greater extent than previous proposals.

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: Financial support: Novartis Korea, Seoul, Korea.

: The sponsor or funding organization had no role in the design or conduct of this research. No conflicting relationship exists for any author.

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Original articleLow-Fluence Photodynamic Therapy versus Ranibizumab for Chronic Central Serous Chorioretinopathy: One-Year Results of a Randomized Trial

Purpose

Design

Participants

Intervention

Main Outcome Measures

Results

Conclusions

Section snippets

Methods

Results

Discussion

Am J Ophthalmol

Am J Ophthalmol

Am J Ophthalmol

Ophthalmology

Diffuse retinal pigment epitheliopathy complicating systemic corticosteroid treatment

Br J Ophthalmol

Pathogenesis of disciform detachment of the neuroepithelium

Am J Ophthalmol

Indocyanine green angiography of central serous chorioretinopathy

Int Ophthalmol

Digital indocyanine green videoangiography of central serous chorioretinopathy

Arch Ophthalmol

Indocyanine green videoangiography of older patients with central serous chorioretinopathy

Retina

Persistent and bilateral choroidal vascular abnormalities in central serous chorioretinopathy

Retina

Choroidal findings in the course of idiopathic serous pigment epithelium detachment detected by indocyanine green videoangiography

Retina

Choroidal vascular remodelling in central serous chorioretinopathy after indocyanine green guided photodynamic therapy with verteporfin: a novel treatment at the primary disease level

Br J Ophthalmol

Photodynamic therapy for chronic central serous chorioretinopathy

Retina

Dose-related structural effects of photodynamic therapy on choroidal and retinal structures of human eyes

Graefes Arch Clin Exp Ophthalmol

Ocular changes after photodynamic therapy

Invest Ophthalmol Vis Sci

Original article
Low-Fluence Photodynamic Therapy versus Ranibizumab for Chronic Central Serous Chorioretinopathy: One-Year Results of a Randomized Trial